The present invention relates to a pharmaceutical composition for administering etanidazole by injection. More particularly, this invention provides solution formulations containing higher concentrations of etanidazole, and having better physical and chemical stability than other known formulations of etanidazole.
Formulations of pharmaceutical compositions and processes for preparing them depend upon the properties of the active ingredient, the desired route of administration and the end use to be obtained. Etanidazole is a substituted nitroimidazole that sensitizes tumor cells to radiation therapy. The compound and methods for its synthesis are described in U.S. Pat. No. 3,679,698. Its use as a radiosensitizing agent is described in U.S. Pat. No. 4,371,540. The preferred route of administration of radiosensitizers is by intravenous injection or infusion. The intravenous route of administration affords rapid delivery of the drug to the target tissue, complete bioavailability, and is more predictable and controllable than other routes. Solution formulations for intravenous administration must be essentially free of particulate matter, and they must be sterile. They must be physically and chemically stable, so that efficacy and safety are predictable. Another property generally needed for cancer chemotherapeutic agents, such as etanidazole, is a high concentration of the active ingredient. This is desirable because therapy is often guided toward the maximum tolerated dose. Etanidazole formulations are subject to all of these requirements.
Formulations for intravenous administration can be prepared as solutions that are ready to inject or ready to dilute with an infusion solution, or they can be prepared as dry powders that must be dissolved before use. Solution formulations are preferred over dry powders, when feasible, because of ease of use, ease of manufacture, and reduced cost.